DESCRIPTION: The general goal of this project is to investigate the energetic basis of all levels of protein structure including specific protein complexes, and determine experimentally the factors responsible for their formation. This requires: (a) estimation of the overall energetic balance of formation of macromolecular structures in aqueous solution by microcalorimetric techniques, and (b) estimation of the hydration component of these energetics by studying the transfer of various compounds modeling protein groups into water. Previously, Dr. Privalov concentrated on studies of the energetics of formation of tertiary structure of globular proteins. He now proposes to extend this approach to the investigation of two other levels of protein structure: the lower level, secondary structure, which will be modeled by synthetic polypeptides, and the higher level, the quaternary structure and specific complexes of proteins with proteins and nucleic acids. Covering all levels of protein structure is required to refine the previously obtained parameters, to investigate the interaction between the various levels of structural organization, and to clarify the physical basis of molecular recognition in biology.